成年大鼠去多巴胺能神经元支配的纹状体和胚胎小鼠腹侧中脑发育的蛋白质组学研究
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摘要
第一部分 帕金森病模型中去神经支配纹状体的蛋白质组学分析
本实验对6-羟基多巴胺帕金森病模型中去神经支配纹状体蛋白质组的表达变化进行了研究。我们发现去多巴胺能神经元支配的纹状体提取液具有促进体外培养的胚胎腹侧中脑多巴胺能神经元存活的作用。为了进一步研究这一营养性作用的分子基础,寻找新的促进多巴胺能神经元损伤修复的因子,本实验利用双相凝胶电泳比较分析了去神经支配后纹状体蛋白质组的表达变化。结果显示,纹状体中绝大多数蛋白质的表达水平在去神经支配后没有明显差异,但少数蛋白质的表达水平发生了明显变化:7个蛋白质表达上升,4个蛋白质表达下降。经过基质辅助激光解析电离-飞行时间质谱确定了其中8个蛋白质的种类,表达水平上调的蛋白质包括:淀粉样蛋白前体蛋白2(amyloid precursor-like protein 2, APLP2), 激肽原(kininogen), 葡萄糖激酶(glucokinase), 脑源一型α原肌球蛋白(tropomyosin αchain type brain-1, TMBR-1), 依钙蛋白Ⅰ轻链(calpactin Ⅰ light chain, Calpactin Ⅰ-lc);表达水平下调的蛋白质包括: 神经表皮生长因子样蛋白2(Neural epidermal growth factor-like 2, Nell 2), 甲状腺素受体β-2(thyroid hormone receptorβ-2, THRβ-2),小染色体维持因子6(Mini-chromosome maintenance 6, MCM6)。免疫组织化学染色表明黑质多巴胺能神经元共表达APLP2和酪氨酸羟化酶。6-羟基多巴胺损毁黑质纹状体通路后,APLP2在黑质致密带的表达随着多巴胺能神经元的死亡而降低,但是在去神经支配的纹状体和黑质网状带中APLP2的表达上升。而且,过表达硫酸软骨素修饰APLP2(APLP2-751)的中国仓鼠卵巢细胞系条件培养液具有促进体外培养的胚胎腹侧中脑多巴胺神经元存活的作用,过表达无硫酸软骨素修饰APLP2(APLP2-763)的中国仓鼠卵巢细胞系条件培养液不具有同样的作用。这些结果提示硫酸软骨素修饰APLP2对于黑质多巴胺能神经元可能具
有保护和促进损伤修复的作用。
During neurodegenerative processes, the injured cells will promote their target tissue to release neurotrophic factors. In this study, we characterized trophic effects of the striatum of adult Sprague-Dawley rat following 6-hydroxydopamine lesions on survival of fetal DA neurons. Treatment of ventral mesencephalic cultures with the striatal extracts delayed DA cell death in dose-dependent manner. In order to better understand the molecular events occurring in the denervated target tissue, we investigated the variations of protein expression in the dopamine-depleted striatum. The rat striatum, ipsilateral to the lesion was analyzed by two-dimensional gel electrophoresis followed by matrix assisted laser desorption/ionization-time of flight mass spectrometry. Seven proteins were up-regulated (188.1-750% compared to control) in response to the lesion, including amyloid precursor-like protein 2 (APLP2), kininogen, glucokinase, tropomyosin α chain, type brain-1 and calpactin Ⅰlight chain; whilst four proteins , including neural epidermal growth factor-like 2, minichromosome maintenance 6, and thyroid hormone receptor β-2, were down-regulated (to between 36% and 59% of levels in sham-operated controls). Three proteins that did not match with available data in the SWISS-PROT protein database were also determined. Immunohistochemical analysis demonstrated colocalization of APLP2 and tyrosine hydroxylase in the nigral neurons. Moreover,
reduction of APLP2-positive neurons in the substantia nigra pars compacta as well as the increases in the substantial nigra pars reticulata and in the striatum were observed. Furthermore, the conditioned medium of the Chinese hamster ovary cells over-expressing APLP2-751 (chondroitin sulphate-modified), but not APLP2-763 (nonchondroitin sulphate-modified), was able to increase the number of the tyrosine hydroxylase-positive neurons in fetal mesencephalic cultures. These results suggest that the expression of APLP2, a protein that has been thought to be associated with Alzheimer’s disease, is up-regulated in the striatum following dopaminergic denervation. They also support the view that chondroitin sulphate-modified APLP2 protein may play an important role in protection and repairation of dopaminergic neuron.
本实验对6-羟基多巴胺帕金森病模型中去神经支配纹状体蛋白质组的表达变化进行了研究。我们发现去多巴胺能神经元支配的纹状体提取液具有促进体外培养的胚胎腹侧中脑多巴胺能神经元存活的作用。为了进一步研究这一营养性作用的分子基础,寻找新的促进多巴胺能神经元损伤修复的因子,本实验利用双相凝胶电泳比较分析了去神经支配后纹状体蛋白质组的表达变化。结果显示,纹状体中绝大多数蛋白质的表达水平在去神经支配后没有明显差异,但少数蛋白质的表达水平发生了明显变化:7个蛋白质表达上升,4个蛋白质表达下降。经过基质辅助激光解析电离-飞行时间质谱确定了其中8个蛋白质的种类,表达水平上调的蛋白质包括:淀粉样蛋白前体蛋白2(amyloid precursor-like protein 2, APLP2), 激肽原(kininogen), 葡萄糖激酶(glucokinase), 脑源一型α原肌球蛋白(tropomyosin αchain type brain-1, TMBR-1), 依钙蛋白Ⅰ轻链(calpactin Ⅰ light chain, Calpactin Ⅰ-lc);表达水平下调的蛋白质包括: 神经表皮生长因子样蛋白2(Neural epidermal growth factor-like 2, Nell 2), 甲状腺素受体β-2(thyroid hormone receptorβ-2, THRβ-2),小染色体维持因子6(Mini-chromosome maintenance 6, MCM6)。免疫组织化学染色表明黑质多巴胺能神经元共表达APLP2和酪氨酸羟化酶。6-羟基多巴胺损毁黑质纹状体通路后,APLP2在黑质致密带的表达随着多巴胺能神经元的死亡而降低,但是在去神经支配的纹状体和黑质网状带中APLP2的表达上升。而且,过表达硫酸软骨素修饰APLP2(APLP2-751)的中国仓鼠卵巢细胞系条件培养液具有促进体外培养的胚胎腹侧中脑多巴胺神经元存活的作用,过表达无硫酸软骨素修饰APLP2(APLP2-763)的中国仓鼠卵巢细胞系条件培养液不具有同样的作用。这些结果提示硫酸软骨素修饰APLP2对于黑质多巴胺能神经元可能具
有保护和促进损伤修复的作用。
During neurodegenerative processes, the injured cells will promote their target tissue to release neurotrophic factors. In this study, we characterized trophic effects of the striatum of adult Sprague-Dawley rat following 6-hydroxydopamine lesions on survival of fetal DA neurons. Treatment of ventral mesencephalic cultures with the striatal extracts delayed DA cell death in dose-dependent manner. In order to better understand the molecular events occurring in the denervated target tissue, we investigated the variations of protein expression in the dopamine-depleted striatum. The rat striatum, ipsilateral to the lesion was analyzed by two-dimensional gel electrophoresis followed by matrix assisted laser desorption/ionization-time of flight mass spectrometry. Seven proteins were up-regulated (188.1-750% compared to control) in response to the lesion, including amyloid precursor-like protein 2 (APLP2), kininogen, glucokinase, tropomyosin α chain, type brain-1 and calpactin Ⅰlight chain; whilst four proteins , including neural epidermal growth factor-like 2, minichromosome maintenance 6, and thyroid hormone receptor β-2, were down-regulated (to between 36% and 59% of levels in sham-operated controls). Three proteins that did not match with available data in the SWISS-PROT protein database were also determined. Immunohistochemical analysis demonstrated colocalization of APLP2 and tyrosine hydroxylase in the nigral neurons. Moreover,
reduction of APLP2-positive neurons in the substantia nigra pars compacta as well as the increases in the substantial nigra pars reticulata and in the striatum were observed. Furthermore, the conditioned medium of the Chinese hamster ovary cells over-expressing APLP2-751 (chondroitin sulphate-modified), but not APLP2-763 (nonchondroitin sulphate-modified), was able to increase the number of the tyrosine hydroxylase-positive neurons in fetal mesencephalic cultures. These results suggest that the expression of APLP2, a protein that has been thought to be associated with Alzheimer’s disease, is up-regulated in the striatum following dopaminergic denervation. They also support the view that chondroitin sulphate-modified APLP2 protein may play an important role in protection and repairation of dopaminergic neuron.
引文
Nowak R. From genome to proteome: looking at a cell’s proteins. Science, 1995, 270:369-371.
Fields S. Proteomics in Genomeland. Science, 2001, 291:1221-1224.
Pander A, Mann M. Proteomics to study genes and genomes. Nature, 2000, 405:837-846.
O’Farrell PH. Hight resolution two-dimensional electrophoresis of proteins. J Biol Chem, 1975, 250:4007-4021.
Gorg A, Obermaier C, Boguth G, Harder A. The current state of two-dimensional electrophoresis with immobilized pH gradients. Electrophoresis, 2000, 21:1037-1053.
Wolters DA, Washburn MP, Yates JR. An automated multidimensional protein identification technology for shotgun proteomics. Anal Chem, 2001, 73: 5683-5690.
Wilm M, Shevchenko A, Houthaeve T, Breit S. Femtomole sequencing of proteins from polyacrylamide gels by nano-electrospray mass spectrometry. Nature, 1996, 379:466-469.
Berndt P, Hobohm U, Langen H. Reliable automatic protein identification from matrix-assisted laser desorption/ionization mass spectrometric peptide fingerprints. Electrophoresis, 1999, 20:3521-3526.
Cahill DJ, Nordhoff E. Protein arrays and their role in proteomics. Adv Biochem Eng Biotechnol, 2003, 83:177-187.
Flory MR, Griffin TJ, Martin D, Aebersold R. Advances in quantitative proteomics using stable isotope tags. Trends Biotechnol, 2002, 20:S23-9.
Hanash S. Disease proteomics. Nature, 2003, 422:226-232.
Hughes AJ, Daniel SE, Blankson S, Lees AJ. A clinicopathologic study of 100 cases of Parkinson's disease. Arch Neurol, 1993, 50:140-148.
Blum D, Torch S, Lambeng N, Nissou M, Benabid AL, Sadoul R, Verna JM.
Molecular pathways involved in the neurotoxicity of 6-OHDA, dopamine and MPTP: contribution to the apoptotic theory in Parkinson's disease. Prog Neurobiol, 2001, 65:135-72.
Espejo M, Cutillas B, Arenas TE, Ambrosio S. Increased survival of dopaminergic neurons in striatal grafts of fetal ventral mesencephalic cells exposed to neurotrophin-3 or glial cell line-derived neurotrophic factor. Cell Transplant, 2000, 9:45-53.
Mufson EJ, Kroin JS, Sendera TJ, Sobreviela T. Distribution and retrograde transport of trophic factors in the central nervous system: functional implications for the treatment of neurodegenerative diseases. Prog Neurobiol, 1999, 57:451-484.
Buckland ME, Cunningham AM. Alterations in the neurotrophic factors BDNF, GDNF and CNTF in the regenerating olfactory system. Ann N Y Acad Sci, 1998, 855:260-265.
Hicks RR, Martin VB, Zhang L, Seroogy KB. Mild experimental brain injury differentially alters the expression of neurotrophin and neurotrophin receptor mRNAs in the hippocampus. Exp Neurol, 1999, 160:469-478.
Asada H, Ip NY, Pan L, Razack N, Parfitt MM, Plunkett RJ. Time course of ciliary neurotrophic factor mRNA expression is coincident with the presence of protoplasmic astrocytes in traumatized rat striatum. J Neurosci Res, 1995, 40:22-30.
Logan A, Frautschy SA, Gonzalez AM, Baird A. A time course for the focal elevation of synthesis of basic fibroblast growth factor and one of its high-affinity receptors (flg) following a localized cortical brain injury. J Neurosci, 1992, 12:3828-3837.
Logan A, Frautschy SA, Gonzalez AM, Sporn MB, Baird A. Enhanced expression of transforming growth factor beta 1 in the rat brain after a localized cerebral injury. Brain Res, 1992, 587:216-225.
Jankowsky JL, Patterson PH. The role of cytokines and growth factors in seizures and their sequelae. Prog Neurobiol, 2001, 63:125-149.
Boyd JG, Gordon T. Glial cell line-derived neurotrophic factor and brain-derived neurotrophic factor sustain the axonal regeneration of chronically axotomized motoneurons in vivo. Exp Neurol, 2003, 183:610-619.
Ando S, Kobayashi S, Waki H, Kon K, Fukui F, Tadenuma T, Iwamoto M, Takeda Y, Izumiyama N, Watanabe K, Nakamura H. Animal model of dementia induced by entorhinal synaptic damage and partial restoration of cognitive deficits by BDNF and carnitine. J Neurosci Res, 2002, 70:519-527.
Parent JM, Yu TW, Leibowitz RT, Geschwind DH, Sloviter RS, Lowenstein DH.
Dentate granule cell neurogenesis is increased by seizures and contributes to aberrant network reorganization in the adult rat hippocampus. J Neurosci, 1997, 17:3727-3738.
Lee J, Seroogy KB, Mattson MP. Dietary restriction enhances neurotrophin expression and neurogenesis in the hippocampus of adult mice. J Neurochem, 2002, 80:539-547.
Ganat Y, Soni S, Chacon M, Schwartz ML, Vaccarino FM. Chronic hypoxia up-regulates fibroblast growth factor ligands in the perinatal brain and induces fibroblast growth factor-responsive radial glial cells in the sub-ependymal zone. Neuroscience, 2002, 112:977-991.
Carvey PM, Ptak LR, Nath ST, Sierens DK, Mufson EJ, Goetz CG, Klawans HL. Striatal extracts from patients with Parkinson's disease promote dopamine neuron growth in mesencephalic cultures. Exp Neurol, 1993,120: 149-152.
Zhou J, Pliego-Rivero B, Bradford HF, Stern G.M. The BDNF content of postnatal and adult rat brain: the effects of 6-hydroxydopamine lesions in adult brain. Developmental Brain Research, 1996, 97:297-303.
Numan S, Seroogy KB. Increased expression of trkB mRNA in rat caudate--putamen following 6-OHDA lesions of the nigrostriatal pathway. Eur J Neurosci, 1997, 9:489-495.
Zhou J, Yu Y, Tang ZS, Shen Y, Xu L. Differential expression of mRNAs of GDNF family in the striatum following 6-OHDA-induced lesion. Neuroreport, 2000, 11:3289-3293.
Ciesielska A, Joniec I, Przybylkowski A, Gromadzka G, Kurkowska-Jastrzebska I, Czlonkowska A, Czlonkowski A. Dynamics of expression of the mRNA for cytokines and inducible nitric synthase in a murine model of the Parkinson's disease. Acta Neurobiol Exp, 2003, 63:117-126.
Nagatsu T, Mogi M, Ichinose H, Togari A. Changes in cytokines and neurotrophins in Parkinson's disease. J Neural Transm Suppl, 2000, 60:277-290.
Krieglstein K, Unsicker K. Transforming growth factor-beta promotes survival of midbrain dopaminergic neurons and protects them against N-methyl-4-phenylpyridinium ion toxicity. Neuroscience, 1994, 63:1189-1196.
Levivier M, Przedborski S, Bencsics C, Kang UJ. Intrastriatal implantation of fibroblasts genetically engineered to produce brain-derived neurotrophic factor prevents degeneration of dopaminergic neurons in a rat model of Parkinson's disease. J Neurosci, 1995, 15:7801–7820.
Wang ZH, Ji Y, Shan W, Zeng B, Raksadawan N, Pastores GM, Wisniewski T, Kolodny EH. Therapeutic effects of astrocytes expressing both tyrosine hydroxylase and brain-derived neurotrophic factor on a rat model of Parkinson's
disease. Neuroscience, 2002, 113:629-640.
Nakajima K, Hida H, Shimano Y, Fujimoto I, Hashitani T, Kumazaki M, Sakurai T, Nishino H. GDNF is a major component of trophic activity in DA-depleted striatum for survival and neurite extension of DAergic neurons. Brain Res, 2001, 916:76-84.
von Coelln R, Unsicker K, Krieglstein K. Screening of interleukins for survival-promoting effects on cultured mesencephalic dopaminergic neurons from embryonic rat brain. Brain Res Dev Brain Res, 1995, 89:150-154.
Ferger B, Rose S, Jenner A, Halliwell B, Jenner P. 6-hydroxydopamine increases hydroxyl free radical production and DNA damage in rat striatum. Neuroreport, 2001, 12:1155-1159.
Kang J, Lemaire HG, Unterbeck A, Salbaum JM, Masters CL, Grzeschik KH, Multhaup G., Beyreuther K, Muller-Hill B. The precursor of Alzheimer's disease amyloid A4 protein resembles a cell-surface receptor. Nature, 1987, 325:733-736.
Wasco W, Bupp K, Magendantz M, Gusella JF, Tanzi RE, Solomon F. Identification of a Mouse Brain cDNA that Encodes a Protein Related to the Alzheimer Disease-Associated Amyloid ? Protein Precursor. Proc Natl Acad Sci USA, 1992, 89:10758-10762.
Wasco W, Gurubhagavatula S, Paradis MD, Romano DM, Sisodia SS, Hyman BT, Neve RL, Tanzi RE. Isolation and characterization of the human APLP2 gene encoding a homologue of the Alzheimer's associated amyloid Beta-protein precursor. Nature Genetics, 1993, 5:95-100.
Goedert M, Sisodia SS, Price DL. Neurofibrillary tangles and beta-amyloid deposits in Alzheimer's disease. Curr Opin Neurobiol, 1991, 1:441-447.
Selkoe DJ. Cell biology of the amyloid beta-protein precursosr and the mechanism of Alzheimer’s disease. Annu Rev Cell Biol, 1994, 10:373-403.
Tanzi RE, McClatchey AI, Lamperti ED, Villa-Komaroff L, Gusella JF, Neve RL. Protease inhibitor domain encoded by an amyloid protein precursor mRNA associated with Alzheimer's disease. Nature, 1988, 331:528-530.
White AR, Reyes R, Mercer JF, Camakaris J, Zheng H, Bush AI, Multhaup G, Beyreuther K, Masters CL, Cappai R. Copper levels are increased in the cerebral cortex and liver of APP and APLP2 knockout mice. Brain Res, 1999, 842:439-444.
Slunt HH, Thinakaran G., von Koch C, Lo ACY, Tanzi R, Sisodia SS. Expression of a ubiquitous, cross-reactive homologue of the mouse beta-amyloid precursor protein (APP). J Biol Chem, 1994, 269:2637-2644.
Thinakaran G, Sisodia SS. Amyloid precursor-like protein 2 (APLP2) is
modified by the addition of chondroitin sulfate glycosaminoglycan at a single site. J Biol Chem, 1994, 269:22099-22104.
Shioi J, Pangalos MN, Ripellino JA, Vassilacopoulou D, Mytilineou C, Margolis RU, Robakis NK. The Alzheimer amyloid precursor proteoglycan (appican) is present in brain and is produced by astrocytes but not by neurons in primary neural cultures. J Biol Chem, 1995, 270:11839-11844.
Thinakaran G., Slunt HH, Sisodia SS. Novel regulation of chondroitin sulfate glycosaminoglycan modification of amyloid precursor protein and its homologue, APLP2. J Biol Chem, 1995, 270:16522-16525.
Webster MT, Groome N, Francis PT, Pearce BR, Sherri E, Thinakaran G, Felsenstein KM, Wasco W, Tanzi RE, Bowen DM. A novel protein, amyloid precursor-like protein 2, is present in human brain, cerebrospinal fluid and conditioned media. Biochem J, 1995, 310:95-99.
Sisodia SS, Thinakaran G, Slunt HH, Kitt CA, von Koch CS, Reed RR, Zheng H. Price DL. Studies on the metabolism and biological function of APLP2. Ann N Y Acad Sci, 1996, 777:77-81.
Thinakaran G., Kitt CA, Roskams AJ, Slunt HH, Masliah E, von Koch C, Ginsberg SD, Ronnett GV, Reed RR, Price DL. Distribution of an APP homolog, APLP2, in the mouse olfactory system: a potential role for APLP2 in axogenesis. J Neurosci, 1995, 15:6314-6326.
von Koch CS, Zheng H, Chen H, Trumbauer M, Thinakaran G., van der Ploeg LH, Price DL, Sisodia SS. Generation of APLP2 KO mice and early postnatal lethality in APLP2/APP double KO mice. Neurobiol. Aging, 1997, 18: 661-669.
Crain BJ, Hu W, Sze CI, Slunt HH, Koo EH, Price DL, Thinakaran G, Sisodia SS. Expression and distribution of amyloid precursor protein-like protein-2 in Alzheimer's disease and in normal brain. Am J Pathol, 1996, 149:1087-1095.
Ungerstedt U, Arbuthnott GW. Quantitative recording of rotational behaviour in rats after 6-hydroxydopamine lesions of the nigrostriatal dopamine system. Brain Res, 1970, 24:485-493.
Zhu YS, Jones SB, Burke RE, Franklin SO, Inturrisi CE. Quantitation of the levels of tyrosine hydroxylase and preproenkephalin mRNAs in nigrostriatal sites after 6-hydroxydopamine lesions. Life Sci, 1993, 52:1577-1584.
Zhou J, Pliego-Rivero B, Bradford HF, Stern GM. The BDNF content of postnatal and adult rat brain: the effects of 6-hydroxydopamine lesions. Dev Brain Res, 1996, 97:297-303.
Bradford MM A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem, 1976, 72:248-254.
Hyman C, Hofer M, Barde YA, Juhasz M, Yancopoulos GD, Squinto SP, Lindsay RM. BDNF is a neurotrophic factor for dopaminergic neurons of the substantia nigra. Nature, 1991, 350:230-232.
Hyman C, Juhasz M, Jackson C, Wright P, Lindsay RM. Overlapping and distinct action of the neurotrophins BDNF, NT-3, and NT-4/5 on cultured dopaminergic and GABAergic neurons of the ventral mesencephalon. J Neurosci, 1994, 14:335-347.
Gharahdaghi F, Weinberg CR, Meagher DA, Imai BS, Mische SM. Mass spectrometric identificatioin of proteins from silver-stained polyacrylamide gel: a method for the removal of silver ions to enhance sensitivity. Electrophoresis, 1999, 20:601-605.
Li XF, Thinakaran G., Sisodia SS. Amyloid precursor-like protein 2 promotes cell migration toward fibronectin and collagen IV. J Biol Chem, 1999, 274:27249-27256.
Parent JM, Yu TW, Leibowitz RT, Geschwind DH, Sloviter RS, Lowenstein DH. Dentate granule cell neurogenesis is increased by seizures and contributes to aberrant network reorganization in the adult rat hippocampus. J Neurosci, 1997, 17:3727-3738.
Nordhoff E, Egelhofer V, Giavalisco P, Eickhoff H, Horn M, Przewieslik T, Theiss D, Schneider U, Lehrach H, Gobom J. Large-gel two-dimensional electrophoresis-matrix assisted laser desorption/ionization-time of flight-mass spectrometry: an analytical challenge for studying complex protein mixtures. Electrophoresis, 2001, 2:2844-2855.
Selkoe DJ. The cell biology of beta-amyloid precursor protein and presenilin in Alzheimer's disease. Trends Cell Biol, 1998, 8:447-453.
Rassoulzadegan M, Yang Y, Cuzin F. APLP2, a member of the Alzheimer precursor protein family, is required for correct genomic segregation in dividing mouse cells. EMBO J, 1998, 17:4647-4656.
Bayer TA, Cappai R, Masters CL, Beyreuther K, Multhaup G. It all sticks together--the APP-related family of proteins and Alzheimer's disease. Mol Psychiatry, 1999, 4: 524-528.
Dodart JC, Mathis C, Ungerer A. The beta-amyloid precursor protein and its derivatives: from biology to learning and memory processes. Rev Neurosci, 2000, 11:75-93.
Coulson EJ, Paliga K, Beyreuther K, Masters CL. What the evolution of the amyloid protein precursor supergene family tells us about its function. Neurochem Int, 2000, 36:175-184.
Wallace W, Ahlers ST, Gotlib J, Bragin V, Sugar J, Gluck R, Shea PA, Davis KL,
Haroutunian V. Amyloid precursor protein in the cerebral cortex is rapidly and persistently induced by loss of subcortical innervation. Proc Natl Acad Sci USA, 1993, 90:8712-8716.
Zhao M, Momma S, Delfani K, Carlen M, Cassidy RM, Johansson CB, Brismar H, Shupliakov O, Frisen J, Janson AM。 Evidence for neurogenesis in the adult mammalian substantia nigra. Proc Natl Acad Sci USA, 2003, 100:7925-30.
Cappai R, Mok SS, Galatis D, Tucker DF, Henry A, Beyreuther K, Small DH, Masters CL. Recombinant human amyloid precursor-like protein 2 (APLP2) expressed in the yeast Pichia pastoris can stimulate neurite outgrowth. FEBS Lett, 1999, 442: 95-98.
Hayashi T, Hotta H, Itoh M, Homma M. Protection of mice by a protease inhibitor, aprotinin, against lethal Sendai virus pneumonia. J General Virol, 1991, 72:979-982.
van Nostrand WE, Schmaier AH, Siegel RS, Wagner SL, Raschke WC. Enhanced plasmin inhibition by a reactive center lysine mutant of the Kunitz-type protease inhibitor domain of the amyloid beta-protein precursor. J Biol Chem, 1995, 270:22827-22830.
Grumet M, Friedlander DR, Sakurai T. Functions of brain chondroitin sulfate proteoglycans during developments: interactions with adhesion molecules. Perspect. Dev Neurobiol, 1996, 3:319-330.
Bovolenta P, Fernaud-Espinosa I. Nervous system proteoglycans as modulators of neurite outgrowth. Prog Neurobiol, 2000, 61:113-132.
Parent A, Hazrati LN. Functional anatomy of the basal gangalia. Part I: The cortico-basal gangalia-thalamo-cortical loop. Brain Res Rev, 1995, 20: 91-127.
Blandini F, Nappi G, Tassorelli C, Martignoni E. Functional changes of the basal ganglia circuitry in Parkinson's disease. Prog Neurobiol, 2000, 62:63-88.
Takano M, Horie M, Narahara M, Miyake M, Okamoto H. Expression of kininogen mRNAs and plasma kallikrein mRNA by cultured neurons, astrocytes and meningeal cells in the rat brain. Immunopharmacology, 1999, 45:121-126.
Li Z, Tyor WR, Xu J, Chao J, Hogan EL. Immunohistochemical localization of kininogen in rat spinal cord and brain. Exp Neurol, 1999, 159:528-537.
Xu J, Hsu CY, Junker H, Chao S, Hogan EL, Chao J. Kininogen and kinin in experimental spinal cord injury. J Neurochem, 1991, 57:975-980.
Ellis EF, Chao J, Heizer ML. Brain kininogen following experimental brain injury: evidence for a secondary event. J Neurosurg, 1989, 71:437-442.
Kos J, Lah TT. Cysteine proteinases and their endogenous inhibitors: target proteins for prognosis, diagnosis and therapy in cancer. Oncol Rep, 1998, 5: 1349-1361.
Das A, Smalheiser NR, Markaryan A, Kaplan A. Evidence for binding of the ectodomain of amyloid precursor protein 695 and activated high molecular weight kininogen. Biochim Biophys Acta, 2002, 1571:225-238.
Printz R, Magnuson MA, Granner DK. Mammalian glucokinase. Annu Rev Nutr. 1993, 13:463 –496.
Matschinsky FM, Ellerman JE. Metabolism of glucose in the islets of Langerhans. J Biol Chem, 1968, 243:2730 –2736.
Dunn-Meynell AA, Routh VH, Kang L, Gaspers L, Levin BE. Glucokinase is the likely mediator of glucosensing in both glucose-excited and glucose-inhibited central neurons. Diabetes, 2002, 51:2056-2065.
Alvarez E, Roncero I, Chowen JA, Vazquez P, Blazquez E. Evidence that glucokinase regulatory protein is expressed and interacts with glucokinase in rat brain. J Neurochem, 2002, 80:45-53.
Roncero I, Alvarez E, Vazquez P, Blazquez E. Functional glucokinase isoforms are expressed in rat brain. J Neurochem, 2000, 74:1848-1857.
Dufour C, Weinberger RP, Gunning P. Tropomyosin isoform diversity and neuronal morphogenesis. Immunol Cell Biol, 1998, 76: 424-429.
Vrhovski B, Schevzov G, Dingle S, Lessard JL, Gunning P, Weinberger RP. Tropomyosin isoforms from the gamma gene differing at the C-terminus are spatially and developmentally regulated in the brain. J Neurosci Res, 2003, 72: 373-383.
Hughes JA, Cooke-Yarborough CM, Chadwick NC, Schevzov G, Arbuckle SM, Gunning P, Weinberger RP. High-molecular-weight tropomyosins localize to the contractile rings of dividing CNS cells but are absent from malignant pediatric and adult CNS tumors. Glia, 2003, 42:25-35.
Masiakowski P, Shooter EM. Nerve growth factor induces the genes for two proteins related to a family of calcium-binding proteins in PC12 cells. Proc Natl Acad Sci USA, 1988, 85:1277-1281.
De Leon M, Van Eldik LJ, Shooter EM. Differential regulation of S100 beta and mRNAs coding for S100-like proteins (42A and 42C) during development and after lesion of rat sciatic nerve. J Neurosci Res, 1991, 29:155-162.
Nelson BR, Matsuhashi S, Lefcort F. Restricted neural epidermal growth factor-like like 2 (NELL2) expression during muscle and neuronal differentiation. Gene Expr Patterns, 2002, 2:7-15.
Kuroda S, Oyasu M, Kawakami M, Kanayama N, Tanizawa K, Saito N, Abe T, Matsuhashi S, Ting K. Biochemical characterization and expression analysis of neural thrombospondin-1-like proteins NELL1 and NELL2. Biochem Biophys Res Commun, 1999, 265:79-86.
Kuroda S, Tanizawa K. Involvement of epidermal growth factor-like domain of NELL proteins in the novel protein-protein interaction with protein kinase C. Biochem Biophys Res Commun, 1999, 265:752-757.
Lechan RM, Qi Y, Berrodin TJ, Davis KD, Schwartz HL, Strait KA, Oppenheimer JH, Lazar MA. Immunocytochemical delineation of thyroid hormone receptor beta 2-like immunoreactivity in the rat central nervous system. Endocrinology, 1993, 132:2461-2469.
Mendez-Pertuz M, Sanchez-Pacheco A, Aranda A. The thyroid hormone receptor antagonizes CREB-mediated transcription. EMBO J, 2003, 22:3102-3112.
Fletcher RJ, Bishop BE, Leon RP, Sclafani RA, Ogata CM, Chen XS.The structure and function of MCM from archaeal M. Thermoautotrophicum. Nat Struct Biol, 2003, 10:160-167.
Labib K, Tercero JA, Diffley JF. Uninterrupted MCM2-7 function required for DNA replication fork progression. Science, 2000, 288:1643-1647.
Zhou J, Yu Y, Tang ZS, Xu L. Differential expression of mRNAs of GDNF family in the striatum following 6-OHDA-induced lesion. Neuroreport, 2000, 11: 3289-3293.
Fields S. Proteomics in Genomeland. Science, 2001, 291:1221-1224.
Pander A, Mann M. Proteomics to study genes and genomes. Nature, 2000, 405:837-846.
O’Farrell PH. Hight resolution two-dimensional electrophoresis of proteins. J Biol Chem, 1975, 250:4007-4021.
Gorg A, Obermaier C, Boguth G, Harder A. The current state of two-dimensional electrophoresis with immobilized pH gradients. Electrophoresis, 2000, 21:1037-1053.
Wolters DA, Washburn MP, Yates JR. An automated multidimensional protein identification technology for shotgun proteomics. Anal Chem, 2001, 73: 5683-5690.
Wilm M, Shevchenko A, Houthaeve T, Breit S. Femtomole sequencing of proteins from polyacrylamide gels by nano-electrospray mass spectrometry. Nature, 1996, 379:466-469.
Berndt P, Hobohm U, Langen H. Reliable automatic protein identification from matrix-assisted laser desorption/ionization mass spectrometric peptide fingerprints. Electrophoresis, 1999, 20:3521-3526.
Cahill DJ, Nordhoff E. Protein arrays and their role in proteomics. Adv Biochem Eng Biotechnol, 2003, 83:177-187.
Flory MR, Griffin TJ, Martin D, Aebersold R. Advances in quantitative proteomics using stable isotope tags. Trends Biotechnol, 2002, 20:S23-9.
Hanash S. Disease proteomics. Nature, 2003, 422:226-232.
Hughes AJ, Daniel SE, Blankson S, Lees AJ. A clinicopathologic study of 100 cases of Parkinson's disease. Arch Neurol, 1993, 50:140-148.
Blum D, Torch S, Lambeng N, Nissou M, Benabid AL, Sadoul R, Verna JM.
Molecular pathways involved in the neurotoxicity of 6-OHDA, dopamine and MPTP: contribution to the apoptotic theory in Parkinson's disease. Prog Neurobiol, 2001, 65:135-72.
Espejo M, Cutillas B, Arenas TE, Ambrosio S. Increased survival of dopaminergic neurons in striatal grafts of fetal ventral mesencephalic cells exposed to neurotrophin-3 or glial cell line-derived neurotrophic factor. Cell Transplant, 2000, 9:45-53.
Mufson EJ, Kroin JS, Sendera TJ, Sobreviela T. Distribution and retrograde transport of trophic factors in the central nervous system: functional implications for the treatment of neurodegenerative diseases. Prog Neurobiol, 1999, 57:451-484.
Buckland ME, Cunningham AM. Alterations in the neurotrophic factors BDNF, GDNF and CNTF in the regenerating olfactory system. Ann N Y Acad Sci, 1998, 855:260-265.
Hicks RR, Martin VB, Zhang L, Seroogy KB. Mild experimental brain injury differentially alters the expression of neurotrophin and neurotrophin receptor mRNAs in the hippocampus. Exp Neurol, 1999, 160:469-478.
Asada H, Ip NY, Pan L, Razack N, Parfitt MM, Plunkett RJ. Time course of ciliary neurotrophic factor mRNA expression is coincident with the presence of protoplasmic astrocytes in traumatized rat striatum. J Neurosci Res, 1995, 40:22-30.
Logan A, Frautschy SA, Gonzalez AM, Baird A. A time course for the focal elevation of synthesis of basic fibroblast growth factor and one of its high-affinity receptors (flg) following a localized cortical brain injury. J Neurosci, 1992, 12:3828-3837.
Logan A, Frautschy SA, Gonzalez AM, Sporn MB, Baird A. Enhanced expression of transforming growth factor beta 1 in the rat brain after a localized cerebral injury. Brain Res, 1992, 587:216-225.
Jankowsky JL, Patterson PH. The role of cytokines and growth factors in seizures and their sequelae. Prog Neurobiol, 2001, 63:125-149.
Boyd JG, Gordon T. Glial cell line-derived neurotrophic factor and brain-derived neurotrophic factor sustain the axonal regeneration of chronically axotomized motoneurons in vivo. Exp Neurol, 2003, 183:610-619.
Ando S, Kobayashi S, Waki H, Kon K, Fukui F, Tadenuma T, Iwamoto M, Takeda Y, Izumiyama N, Watanabe K, Nakamura H. Animal model of dementia induced by entorhinal synaptic damage and partial restoration of cognitive deficits by BDNF and carnitine. J Neurosci Res, 2002, 70:519-527.
Parent JM, Yu TW, Leibowitz RT, Geschwind DH, Sloviter RS, Lowenstein DH.
Dentate granule cell neurogenesis is increased by seizures and contributes to aberrant network reorganization in the adult rat hippocampus. J Neurosci, 1997, 17:3727-3738.
Lee J, Seroogy KB, Mattson MP. Dietary restriction enhances neurotrophin expression and neurogenesis in the hippocampus of adult mice. J Neurochem, 2002, 80:539-547.
Ganat Y, Soni S, Chacon M, Schwartz ML, Vaccarino FM. Chronic hypoxia up-regulates fibroblast growth factor ligands in the perinatal brain and induces fibroblast growth factor-responsive radial glial cells in the sub-ependymal zone. Neuroscience, 2002, 112:977-991.
Carvey PM, Ptak LR, Nath ST, Sierens DK, Mufson EJ, Goetz CG, Klawans HL. Striatal extracts from patients with Parkinson's disease promote dopamine neuron growth in mesencephalic cultures. Exp Neurol, 1993,120: 149-152.
Zhou J, Pliego-Rivero B, Bradford HF, Stern G.M. The BDNF content of postnatal and adult rat brain: the effects of 6-hydroxydopamine lesions in adult brain. Developmental Brain Research, 1996, 97:297-303.
Numan S, Seroogy KB. Increased expression of trkB mRNA in rat caudate--putamen following 6-OHDA lesions of the nigrostriatal pathway. Eur J Neurosci, 1997, 9:489-495.
Zhou J, Yu Y, Tang ZS, Shen Y, Xu L. Differential expression of mRNAs of GDNF family in the striatum following 6-OHDA-induced lesion. Neuroreport, 2000, 11:3289-3293.
Ciesielska A, Joniec I, Przybylkowski A, Gromadzka G, Kurkowska-Jastrzebska I, Czlonkowska A, Czlonkowski A. Dynamics of expression of the mRNA for cytokines and inducible nitric synthase in a murine model of the Parkinson's disease. Acta Neurobiol Exp, 2003, 63:117-126.
Nagatsu T, Mogi M, Ichinose H, Togari A. Changes in cytokines and neurotrophins in Parkinson's disease. J Neural Transm Suppl, 2000, 60:277-290.
Krieglstein K, Unsicker K. Transforming growth factor-beta promotes survival of midbrain dopaminergic neurons and protects them against N-methyl-4-phenylpyridinium ion toxicity. Neuroscience, 1994, 63:1189-1196.
Levivier M, Przedborski S, Bencsics C, Kang UJ. Intrastriatal implantation of fibroblasts genetically engineered to produce brain-derived neurotrophic factor prevents degeneration of dopaminergic neurons in a rat model of Parkinson's disease. J Neurosci, 1995, 15:7801–7820.
Wang ZH, Ji Y, Shan W, Zeng B, Raksadawan N, Pastores GM, Wisniewski T, Kolodny EH. Therapeutic effects of astrocytes expressing both tyrosine hydroxylase and brain-derived neurotrophic factor on a rat model of Parkinson's
disease. Neuroscience, 2002, 113:629-640.
Nakajima K, Hida H, Shimano Y, Fujimoto I, Hashitani T, Kumazaki M, Sakurai T, Nishino H. GDNF is a major component of trophic activity in DA-depleted striatum for survival and neurite extension of DAergic neurons. Brain Res, 2001, 916:76-84.
von Coelln R, Unsicker K, Krieglstein K. Screening of interleukins for survival-promoting effects on cultured mesencephalic dopaminergic neurons from embryonic rat brain. Brain Res Dev Brain Res, 1995, 89:150-154.
Ferger B, Rose S, Jenner A, Halliwell B, Jenner P. 6-hydroxydopamine increases hydroxyl free radical production and DNA damage in rat striatum. Neuroreport, 2001, 12:1155-1159.
Kang J, Lemaire HG, Unterbeck A, Salbaum JM, Masters CL, Grzeschik KH, Multhaup G., Beyreuther K, Muller-Hill B. The precursor of Alzheimer's disease amyloid A4 protein resembles a cell-surface receptor. Nature, 1987, 325:733-736.
Wasco W, Bupp K, Magendantz M, Gusella JF, Tanzi RE, Solomon F. Identification of a Mouse Brain cDNA that Encodes a Protein Related to the Alzheimer Disease-Associated Amyloid ? Protein Precursor. Proc Natl Acad Sci USA, 1992, 89:10758-10762.
Wasco W, Gurubhagavatula S, Paradis MD, Romano DM, Sisodia SS, Hyman BT, Neve RL, Tanzi RE. Isolation and characterization of the human APLP2 gene encoding a homologue of the Alzheimer's associated amyloid Beta-protein precursor. Nature Genetics, 1993, 5:95-100.
Goedert M, Sisodia SS, Price DL. Neurofibrillary tangles and beta-amyloid deposits in Alzheimer's disease. Curr Opin Neurobiol, 1991, 1:441-447.
Selkoe DJ. Cell biology of the amyloid beta-protein precursosr and the mechanism of Alzheimer’s disease. Annu Rev Cell Biol, 1994, 10:373-403.
Tanzi RE, McClatchey AI, Lamperti ED, Villa-Komaroff L, Gusella JF, Neve RL. Protease inhibitor domain encoded by an amyloid protein precursor mRNA associated with Alzheimer's disease. Nature, 1988, 331:528-530.
White AR, Reyes R, Mercer JF, Camakaris J, Zheng H, Bush AI, Multhaup G, Beyreuther K, Masters CL, Cappai R. Copper levels are increased in the cerebral cortex and liver of APP and APLP2 knockout mice. Brain Res, 1999, 842:439-444.
Slunt HH, Thinakaran G., von Koch C, Lo ACY, Tanzi R, Sisodia SS. Expression of a ubiquitous, cross-reactive homologue of the mouse beta-amyloid precursor protein (APP). J Biol Chem, 1994, 269:2637-2644.
Thinakaran G, Sisodia SS. Amyloid precursor-like protein 2 (APLP2) is
modified by the addition of chondroitin sulfate glycosaminoglycan at a single site. J Biol Chem, 1994, 269:22099-22104.
Shioi J, Pangalos MN, Ripellino JA, Vassilacopoulou D, Mytilineou C, Margolis RU, Robakis NK. The Alzheimer amyloid precursor proteoglycan (appican) is present in brain and is produced by astrocytes but not by neurons in primary neural cultures. J Biol Chem, 1995, 270:11839-11844.
Thinakaran G., Slunt HH, Sisodia SS. Novel regulation of chondroitin sulfate glycosaminoglycan modification of amyloid precursor protein and its homologue, APLP2. J Biol Chem, 1995, 270:16522-16525.
Webster MT, Groome N, Francis PT, Pearce BR, Sherri E, Thinakaran G, Felsenstein KM, Wasco W, Tanzi RE, Bowen DM. A novel protein, amyloid precursor-like protein 2, is present in human brain, cerebrospinal fluid and conditioned media. Biochem J, 1995, 310:95-99.
Sisodia SS, Thinakaran G, Slunt HH, Kitt CA, von Koch CS, Reed RR, Zheng H. Price DL. Studies on the metabolism and biological function of APLP2. Ann N Y Acad Sci, 1996, 777:77-81.
Thinakaran G., Kitt CA, Roskams AJ, Slunt HH, Masliah E, von Koch C, Ginsberg SD, Ronnett GV, Reed RR, Price DL. Distribution of an APP homolog, APLP2, in the mouse olfactory system: a potential role for APLP2 in axogenesis. J Neurosci, 1995, 15:6314-6326.
von Koch CS, Zheng H, Chen H, Trumbauer M, Thinakaran G., van der Ploeg LH, Price DL, Sisodia SS. Generation of APLP2 KO mice and early postnatal lethality in APLP2/APP double KO mice. Neurobiol. Aging, 1997, 18: 661-669.
Crain BJ, Hu W, Sze CI, Slunt HH, Koo EH, Price DL, Thinakaran G, Sisodia SS. Expression and distribution of amyloid precursor protein-like protein-2 in Alzheimer's disease and in normal brain. Am J Pathol, 1996, 149:1087-1095.
Ungerstedt U, Arbuthnott GW. Quantitative recording of rotational behaviour in rats after 6-hydroxydopamine lesions of the nigrostriatal dopamine system. Brain Res, 1970, 24:485-493.
Zhu YS, Jones SB, Burke RE, Franklin SO, Inturrisi CE. Quantitation of the levels of tyrosine hydroxylase and preproenkephalin mRNAs in nigrostriatal sites after 6-hydroxydopamine lesions. Life Sci, 1993, 52:1577-1584.
Zhou J, Pliego-Rivero B, Bradford HF, Stern GM. The BDNF content of postnatal and adult rat brain: the effects of 6-hydroxydopamine lesions. Dev Brain Res, 1996, 97:297-303.
Bradford MM A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem, 1976, 72:248-254.
Hyman C, Hofer M, Barde YA, Juhasz M, Yancopoulos GD, Squinto SP, Lindsay RM. BDNF is a neurotrophic factor for dopaminergic neurons of the substantia nigra. Nature, 1991, 350:230-232.
Hyman C, Juhasz M, Jackson C, Wright P, Lindsay RM. Overlapping and distinct action of the neurotrophins BDNF, NT-3, and NT-4/5 on cultured dopaminergic and GABAergic neurons of the ventral mesencephalon. J Neurosci, 1994, 14:335-347.
Gharahdaghi F, Weinberg CR, Meagher DA, Imai BS, Mische SM. Mass spectrometric identificatioin of proteins from silver-stained polyacrylamide gel: a method for the removal of silver ions to enhance sensitivity. Electrophoresis, 1999, 20:601-605.
Li XF, Thinakaran G., Sisodia SS. Amyloid precursor-like protein 2 promotes cell migration toward fibronectin and collagen IV. J Biol Chem, 1999, 274:27249-27256.
Parent JM, Yu TW, Leibowitz RT, Geschwind DH, Sloviter RS, Lowenstein DH. Dentate granule cell neurogenesis is increased by seizures and contributes to aberrant network reorganization in the adult rat hippocampus. J Neurosci, 1997, 17:3727-3738.
Nordhoff E, Egelhofer V, Giavalisco P, Eickhoff H, Horn M, Przewieslik T, Theiss D, Schneider U, Lehrach H, Gobom J. Large-gel two-dimensional electrophoresis-matrix assisted laser desorption/ionization-time of flight-mass spectrometry: an analytical challenge for studying complex protein mixtures. Electrophoresis, 2001, 2:2844-2855.
Selkoe DJ. The cell biology of beta-amyloid precursor protein and presenilin in Alzheimer's disease. Trends Cell Biol, 1998, 8:447-453.
Rassoulzadegan M, Yang Y, Cuzin F. APLP2, a member of the Alzheimer precursor protein family, is required for correct genomic segregation in dividing mouse cells. EMBO J, 1998, 17:4647-4656.
Bayer TA, Cappai R, Masters CL, Beyreuther K, Multhaup G. It all sticks together--the APP-related family of proteins and Alzheimer's disease. Mol Psychiatry, 1999, 4: 524-528.
Dodart JC, Mathis C, Ungerer A. The beta-amyloid precursor protein and its derivatives: from biology to learning and memory processes. Rev Neurosci, 2000, 11:75-93.
Coulson EJ, Paliga K, Beyreuther K, Masters CL. What the evolution of the amyloid protein precursor supergene family tells us about its function. Neurochem Int, 2000, 36:175-184.
Wallace W, Ahlers ST, Gotlib J, Bragin V, Sugar J, Gluck R, Shea PA, Davis KL,
Haroutunian V. Amyloid precursor protein in the cerebral cortex is rapidly and persistently induced by loss of subcortical innervation. Proc Natl Acad Sci USA, 1993, 90:8712-8716.
Zhao M, Momma S, Delfani K, Carlen M, Cassidy RM, Johansson CB, Brismar H, Shupliakov O, Frisen J, Janson AM。 Evidence for neurogenesis in the adult mammalian substantia nigra. Proc Natl Acad Sci USA, 2003, 100:7925-30.
Cappai R, Mok SS, Galatis D, Tucker DF, Henry A, Beyreuther K, Small DH, Masters CL. Recombinant human amyloid precursor-like protein 2 (APLP2) expressed in the yeast Pichia pastoris can stimulate neurite outgrowth. FEBS Lett, 1999, 442: 95-98.
Hayashi T, Hotta H, Itoh M, Homma M. Protection of mice by a protease inhibitor, aprotinin, against lethal Sendai virus pneumonia. J General Virol, 1991, 72:979-982.
van Nostrand WE, Schmaier AH, Siegel RS, Wagner SL, Raschke WC. Enhanced plasmin inhibition by a reactive center lysine mutant of the Kunitz-type protease inhibitor domain of the amyloid beta-protein precursor. J Biol Chem, 1995, 270:22827-22830.
Grumet M, Friedlander DR, Sakurai T. Functions of brain chondroitin sulfate proteoglycans during developments: interactions with adhesion molecules. Perspect. Dev Neurobiol, 1996, 3:319-330.
Bovolenta P, Fernaud-Espinosa I. Nervous system proteoglycans as modulators of neurite outgrowth. Prog Neurobiol, 2000, 61:113-132.
Parent A, Hazrati LN. Functional anatomy of the basal gangalia. Part I: The cortico-basal gangalia-thalamo-cortical loop. Brain Res Rev, 1995, 20: 91-127.
Blandini F, Nappi G, Tassorelli C, Martignoni E. Functional changes of the basal ganglia circuitry in Parkinson's disease. Prog Neurobiol, 2000, 62:63-88.
Takano M, Horie M, Narahara M, Miyake M, Okamoto H. Expression of kininogen mRNAs and plasma kallikrein mRNA by cultured neurons, astrocytes and meningeal cells in the rat brain. Immunopharmacology, 1999, 45:121-126.
Li Z, Tyor WR, Xu J, Chao J, Hogan EL. Immunohistochemical localization of kininogen in rat spinal cord and brain. Exp Neurol, 1999, 159:528-537.
Xu J, Hsu CY, Junker H, Chao S, Hogan EL, Chao J. Kininogen and kinin in experimental spinal cord injury. J Neurochem, 1991, 57:975-980.
Ellis EF, Chao J, Heizer ML. Brain kininogen following experimental brain injury: evidence for a secondary event. J Neurosurg, 1989, 71:437-442.
Kos J, Lah TT. Cysteine proteinases and their endogenous inhibitors: target proteins for prognosis, diagnosis and therapy in cancer. Oncol Rep, 1998, 5: 1349-1361.
Das A, Smalheiser NR, Markaryan A, Kaplan A. Evidence for binding of the ectodomain of amyloid precursor protein 695 and activated high molecular weight kininogen. Biochim Biophys Acta, 2002, 1571:225-238.
Printz R, Magnuson MA, Granner DK. Mammalian glucokinase. Annu Rev Nutr. 1993, 13:463 –496.
Matschinsky FM, Ellerman JE. Metabolism of glucose in the islets of Langerhans. J Biol Chem, 1968, 243:2730 –2736.
Dunn-Meynell AA, Routh VH, Kang L, Gaspers L, Levin BE. Glucokinase is the likely mediator of glucosensing in both glucose-excited and glucose-inhibited central neurons. Diabetes, 2002, 51:2056-2065.
Alvarez E, Roncero I, Chowen JA, Vazquez P, Blazquez E. Evidence that glucokinase regulatory protein is expressed and interacts with glucokinase in rat brain. J Neurochem, 2002, 80:45-53.
Roncero I, Alvarez E, Vazquez P, Blazquez E. Functional glucokinase isoforms are expressed in rat brain. J Neurochem, 2000, 74:1848-1857.
Dufour C, Weinberger RP, Gunning P. Tropomyosin isoform diversity and neuronal morphogenesis. Immunol Cell Biol, 1998, 76: 424-429.
Vrhovski B, Schevzov G, Dingle S, Lessard JL, Gunning P, Weinberger RP. Tropomyosin isoforms from the gamma gene differing at the C-terminus are spatially and developmentally regulated in the brain. J Neurosci Res, 2003, 72: 373-383.
Hughes JA, Cooke-Yarborough CM, Chadwick NC, Schevzov G, Arbuckle SM, Gunning P, Weinberger RP. High-molecular-weight tropomyosins localize to the contractile rings of dividing CNS cells but are absent from malignant pediatric and adult CNS tumors. Glia, 2003, 42:25-35.
Masiakowski P, Shooter EM. Nerve growth factor induces the genes for two proteins related to a family of calcium-binding proteins in PC12 cells. Proc Natl Acad Sci USA, 1988, 85:1277-1281.
De Leon M, Van Eldik LJ, Shooter EM. Differential regulation of S100 beta and mRNAs coding for S100-like proteins (42A and 42C) during development and after lesion of rat sciatic nerve. J Neurosci Res, 1991, 29:155-162.
Nelson BR, Matsuhashi S, Lefcort F. Restricted neural epidermal growth factor-like like 2 (NELL2) expression during muscle and neuronal differentiation. Gene Expr Patterns, 2002, 2:7-15.
Kuroda S, Oyasu M, Kawakami M, Kanayama N, Tanizawa K, Saito N, Abe T, Matsuhashi S, Ting K. Biochemical characterization and expression analysis of neural thrombospondin-1-like proteins NELL1 and NELL2. Biochem Biophys Res Commun, 1999, 265:79-86.
Kuroda S, Tanizawa K. Involvement of epidermal growth factor-like domain of NELL proteins in the novel protein-protein interaction with protein kinase C. Biochem Biophys Res Commun, 1999, 265:752-757.
Lechan RM, Qi Y, Berrodin TJ, Davis KD, Schwartz HL, Strait KA, Oppenheimer JH, Lazar MA. Immunocytochemical delineation of thyroid hormone receptor beta 2-like immunoreactivity in the rat central nervous system. Endocrinology, 1993, 132:2461-2469.
Mendez-Pertuz M, Sanchez-Pacheco A, Aranda A. The thyroid hormone receptor antagonizes CREB-mediated transcription. EMBO J, 2003, 22:3102-3112.
Fletcher RJ, Bishop BE, Leon RP, Sclafani RA, Ogata CM, Chen XS.The structure and function of MCM from archaeal M. Thermoautotrophicum. Nat Struct Biol, 2003, 10:160-167.
Labib K, Tercero JA, Diffley JF. Uninterrupted MCM2-7 function required for DNA replication fork progression. Science, 2000, 288:1643-1647.
Zhou J, Yu Y, Tang ZS, Xu L. Differential expression of mRNAs of GDNF family in the striatum following 6-OHDA-induced lesion. Neuroreport, 2000, 11: 3289-3293.